HCV disease burden and population segments in Switzerland.

BACKGROUND: Switzerland has made strides towards hepatitis C virus elimination, but as of 2019, elimination was not guaranteed. However, political interest in viral hepatitis has been increasing. We sought to develop a better understanding of Switzerland's progress towards HCV elimination and the profile of remaining HCV-RNA-positive patients. METHODS: A previously described Markov model was updated with recent diagnosis and treatment data and run to generate new forecasts for HCV disease burden. Two scenarios were developed to evaluate HCV morbidity and mortality under the status quo and a scenario that achieves the Swiss Hepatitis Strategy Elimination targets. Next, an analysis was conducted to identify population segments bearing a high burden of disease, where future elimination efforts could be directed. RESULTS: At the beginning of 2020, an estimated 32 100 viremic infections remained in Switzerland (0.37% viremic prevalence). Adult (≥18 years of age) permanent residents born abroad represented the largest subpopulation, accounting for 56% of HCV infections. Thirteen countries accounted for ≥60% of viremic infections amongst permanent residents born abroad, with most people currently residing in Zurich, Vaud, Geneva, Bern, Aargau and Ticino. Amongst Swiss-born HCV-RNA-positive persons, two-thirds had a history of IDU, corresponding to 33% of total infections. CONCLUSIONS: In Switzerland, extra efforts for diagnosis and linkage to care are warranted in foreign-born populations and people with a history of drug use. Population-level measures (eg increasing the number of providers, increase screening) can identify patients who may have otherwise fallen through the gaps or avoided care because of stigma.

Progress toward implementing the Swiss Hepatitis Strategy: Is HCV elimination possible by 2030?

Catalyzed by the concerns over the growing public health and economic burden of Hepatitis C virus (HCV) in Switzerland, a diverse group of experts and patient representatives came together in 2014 to develop the Swiss Hepatitis Strategy, setting targets for the elimination of viral hepatitis in Switzerland by 2030. Previous studies have reported the estimated number of chronic HCV infections and forecasted burden of disease given different intervention strategies. However, given new prevalence data by the Swiss Federal Office of Public Health, which decreased total infections by about half, an updated analysis is warranted. We aimed to provide an updated viremic prevalence estimate for Switzerland and evaluate the impact on forecasted liver related morbidity and mortality of an 'inaction' scenario and intervention scenarios to achieve the Global Health Sector Strategy for Viral Hepatitis and Swiss Hepatitis Strategy goals by 2030. A Markov disease-progression model was used to calculate the present and future burden of HCV infection by disease stage according to these different strategies. In 2017, there were an estimated 36,800 (95% UI: 26,900-39,200) viremic infections in Switzerland. Given the current standard of care, total viremic infections are expected to decline by 45%, while cases of decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths will decrease by 20%. If treatment and diagnosis efforts were to cease in 2018, late stage HCV-related morbidity and mortality would increase by 90-100% by 2030. Increasing treatment and diagnosis to achieve the Global Health Sector Strategy or Swiss Hepatitis Strategy goals by 2030, will reduce the number of chronic infections to less than 13,000 and 4,000, respectively. Although the HCV epidemic is declining in Switzerland, efforts to expand diagnosis and treatment are needed to achieve elimination by 2030.

Hepatitis C virus dynamics among intravenous drug users suggest that an annual treatment uptake above 10% would eliminate the disease by 2030.

BACKGROUND AND AIMS: In Switzerland, the prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) has been decreasing owing to active harm reduction efforts and an aging population. Recent advances in HCV therapeutics may provide an opportunity to direct treatment to high-risk populations, with a goal of reducing HCV prevalence and preventing new infections. In order to guide these efforts, the current project was undertaken with the following aims: (1) to develop a simple model to estimate the number of new HCV infections using available data on PWID; (2) to examine the impact of intervention strategies (prevention and treatment) on new and total HCV infections among PWID. METHODS: A dynamic HCV transmission model was used to track HCV incidence and prevalence among active PWID according to their harm reduction status. The relative impact of treating 1, 5, 10 or 15% of HCV+ PWID with new oral direct acting antivirals was considered. RESULTS: In 2015, there were an estimated 10 160 active PWID in Switzerland, more than 85% of whom were engaged in harm reduction programmes. Approximately 42% of active PWID were HCV-RNA+, with 55 new viraemic infections occurring annually. By 2030, a 60% reduction in the HCV+ PWID population would be expected. In the absence of behavioural changes, the number of secondary infections would increase under all treatment scenarios. With high level treatment, the number of secondary infections would peak and then drop, corresponding to depletion of the viral pool. In Switzerland, 5% treatment of the 2015 HCV+ PWID population per year would result in a 95% reduction in total cases by 2030, whereas ≥10% treatment would result in a >99% reduction. CONCLUSIONS: Timely treatment of hepatitis C virus among people who inject drugs is necessary to reduce the prevalence and prevent new infections in Switzerland.

Innovative sources for funding of viral hepatitis prevention and treatment in low- and middle-income countries: a roundtable meeting report.

Hepatitis B is preventable and hepatitis C is treatable even if still at a high cost; most people who are infected with hepatitis B or C virus have not been screened yet and are unaware of their infections; and most countries, especially developing countries, do not have a national plan to prevent and control viral hepatitis. The advent of effective new treatments for hepatitis C has been an agent of change, allowing consideration of the feasibility of eliminating that disease and accelerating the control of viral hepatitis generally. These facts inspired the Viral Hepatitis Prevention Board (VHPB) to organize a meeting in London (8-9 June 2015) on innovative sources for funding of viral hepatitis prevention and treatment in low- and middle-income countries. The main focus of the meeting was to provide an overview of current health systems controlling viral hepatitis in low- and middle-income countries (LMICs); to identify ways to increase political commitment and financial sustainability of viral hepatitis prevention and control programmes in such countries; to identify potential funders and explore new funding mechanisms; to discuss lessons learnt about funding other disease programmes; to investigate how to convince and motivate decision-makers to fund viral hepatitis programmes in LMICs; to provide options for improving access to affordable screening and treatment of viral hepatitis in LMICs; and to list the commitments required for funding by donors, including governments, bilateral and multilateral organizations, non-traditional donors, development banks, foundations, and commercial financial institutions. To improve viral hepatitis prevention and treatment in LMICs participating hepatitis and financing experts identified the most urgent needs. Data on burden of disease must be improved. Comprehensive hepatitis policies and strategies should be drafted and implemented, and existing strategies and policies improved to increase access to treatment and prevention. Strong political will and leadership should be generated, potential partners identified and partnerships created. Potential funders and funding mechanisms have to be researched. The outcome of this meeting was integrated in a VHPB project to investigate creative financing solutions to expand access to and provision of screening and other preventive services, treatment and care of hepatitis B and C in LMICs. The report is available on www.vhpb.org.

Birth cohort distribution and screening for viraemic hepatitis C virus infections in Switzerland.

OBJECTIVE: In Switzerland, fewer than 40% of hepatitis C virus (HCV) infected individuals have been diagnosed. The aim of this project was to analyse the distribution of HCV cases in order to develop better detection strategies. STUDY DESIGN: Historical data on the HCV-infected population in Switzerland were obtained from published literature, unpublished data and government reports. A disease progression model was used to age the infected population to 2015. The HCV distribution was then used to identify 5-year age cohorts with the highest HCV prevalence. The estimated number of cases needed to screen within an age cohort was calculated using the estimated viraemic prevalence, removing the percent previously diagnosed. RESULTS: In 2015, the median age of the viraemic HCV infected population was 49 years, with 75% of the population born between 1951 and 1985. Random screening of the general population could identify one new viraemic HCV case per 159 persons screened, compared with targeted birth cohort screening, which could identify one new viraemic HCV case per 90-99 persons screened. CONCLUSION: Considering only the direct cost of screening and treatment informing tests, targeted screening by birth cohort is more effective and cost effective than random screening in the general population.

Modeling the Health and Economic Burden of Hepatitis C Virus in Switzerland.

BACKGROUND: Chronic hepatitis C virus infection is a major cause of liver disease in Switzerland and carries a significant cost burden. Currently, only conservative strategies are in place to mitigate the burden of hepatitis C in Switzerland. This study expands on previously described modeling efforts to explore the impact of: no treatment, and treatment to reduce HCC and mortality. Furthermore, the costs associated with untreated HCV were modeled. METHODS: Hepatitis C disease progression and mortality were modeled. Baseline historical assumptions were collected from the literature and expert interviews and strategies were developed to show the impact of different levels of intervention (improved drug cure rates, treatment and diagnosis) until 2030. RESULTS: Under the historical standard of care, the number of advanced stage cases was projected to increase until 2030, at which point the annual economic burden of untreated viremic infections was projected to reach €96.8 (95% Uncertainty Interval: €36 - €232) million. Scenarios to reduce HCV liver-related mortality by 90% by 2030 required treatment of 4,190 ≥F2 or 3,200 ≥F3 patients annually by 2018 using antivirals with a 95% efficacy rate. Delaying the implementation of these scenarios by 2 or 5 years reduced the impact on mortality to 75% and 57%, respectively. CONCLUSIONS: With today's treatment efficacy and uptake rates, hepatitis C disease burden is expected to increase through 2030. A substantial reduction in disease burden can be achieved by means of both higher efficacy drugs and increased treatment uptake. However, these efforts cannot be undertaken without a simultaneous effort to diagnose more infections.

Cost-effectiveness analysis of sofosbuvir compared to current standard treatment in Swiss patients with chronic hepatitis C.

In clinical trials, sofosbuvir showed high antiviral activity in patients infected with hepatitis C virus (HCV) across all genotypes. We aimed to determine the cost-effectiveness of sofosbuvir-based treatment compared to current standard treatment in mono-infected patients with chronic hepatitis C (CHC) genotypes 1-4 in Switzerland. Cost-effectiveness was modelled from the perspective of the Swiss health care system using a lifetime Markov model. Incremental cost-effectiveness ratios (ICERs) used an endpoint of cost per quality-adjusted life year (QALY) gained. Treatment characteristics, quality of life, and transition probabilities were obtained from published literature. Country-specific model inputs such as patient characteristics, mortality and costs were obtained from Swiss sources. We performed extensive sensitivity analyses. Costs and effects were discounted at 3% (range: 0-5%) per year. Sofosbuvir-containing treatment in mixed cohorts of cirrhotic and non-cirrhotic patients with CHC genotypes 1-4 showed ICERs between CHF 10,337 and CHF 91,570 per QALY gained. In subgroup analyses, sofosbuvir dominated telaprevir- and boceprevir-containing treatment in treatment-naïve genotype 1 cirrhotic patients. ICERs of sofosbuvir were above CHF 100,000 per QALY in treatment-naïve, interferon eligible, non-cirrhotic patients infected with genotypes 2 or 3. In deterministic and probabilistic sensitivity analyses, results were generally robust. From a Swiss health care system perspective, treatment of mixed cohorts of cirrhotic and non-cirrhotic patients with CHC genotypes 1-4 with sofosbuvir-containing treatment versus standard treatment would be cost-effective if a threshold of CHF 100,000 per QALY was assumed.

Hepatitis B and C in Switzerland - healthcare provider initiated testing for chronic hepatitis B and C infection.

Hepatitis B and hepatitis C are contagious liver diseases caused by the hepatitis B virus (HBV) and the hepatitis C virus (HCV), respectively. In particular, chronic infection with HBV or HCV is a major public health problem throughout Europe. The majority of persons chronically infected (65%-75%) are not aware of their infection status until symptoms of advanced liver disease appear. In addition, the peak in the number of patients suffering from advanced stages of the disease, such as cirrhosis and hepatocellular carcinoma, has not yet been reached. In order to reduce the current and future morbidity and mortality associated with chronic HBV or HCV infection, the timely detection of chronically infected persons, with follow-up and case management, is crucial. However, the current screening strategies in Europe and Switzerland have to be considered as inadequate to detect the majority of chronically infected persons. Hence, we emphasise the importance of an alternative approach: the healthcare provider initiated identification of HBV or HCV infection in defined risk groups. This entails determining whether a person is not only at risk of being chronically infected, but also at risk of becoming infected with HBV or HCV and, if necessary, testing for HBV or HCV infection.

Viral hepatitis: global goals for vaccination.

In countries where hepatitis A is highly endemic, exposure to hepatitis A virus (HAV) is almost universal before the age of 10 years, and large-scale immunization efforts are not required. In contrast, in areas of intermediate endemicity or in transition from high to intermediate endemicity, where transmission occurs primarily from person to person in the general community (often with periodic outbreaks), control of hepatitis A may be achieved through widespread vaccination programmes. Hepatitis B virus (HBV) is one of the world's most widespread infectious agents and the cause of millions of infections each year. Between 500,000 and 700,000 people die each year from chronic infection-related cirrhosis, hepatocellular carcinoma (HCC) or from acute hepatitis B. Hepatitis B vaccine provides protection against infection and its complications including liver cirrhosis and HCC. It is therefore, the first vaccine against a cancer, the first vaccine protecting from a sexually transmitted infection, and the first vaccine against a chronic disease ever licensed. Control and significant reduction in incidence of new HBV infections as well as hepatocellular carcinoma has repeatedly been reported in countries in East Asia (i.e. Taiwan) and Africa (i.e. The Gambia). Two experimental vaccines against hepatitis E have been developed; one of them has been recently licensed but is not yet widely available. Attempts to develop a hepatitis C vaccine were so far unsuccessful.

Treatment of chronic hepatitis B virus infection in resource-constrained settings: expert panel consensus.

Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource-constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV-related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20-30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV-infected persons in Africa who are co-infected with HBV. Progressive liver disease has been shown to occur in co-infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV-infected persons should be screened for HBV infection; HIV/HBV co-infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource-constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource-constrained settings.

WITHDRAWN: Viral Hepatitis: global goals for vaccination.

This article has been withdrawn at the request of the author. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

The global burden of hepatitis C.

Hepatitis C is of concern both to industrialized and developing countries. Preliminary unpublished estimates of the global burden of disease (GBD) attributable to HCV-related chronic liver disease seem to be substantial. Therefore, the reduction of global mortality and morbidity related to chronic hepatitis C should be a concern to public health authorities, and primary, secondary and tertiary prevention activities should be implemented and monitored in each country, with precise targets set to be reached. In order to decide on national health policies, there is a need to estimate the burden of disease, globally, regionally and nationally. To evaluate the GBD, three components have to be assessed: 1) The global, regional and national burden of morbidity and mortality associated with HCV infection, based on prevalence, incidence, transmission and economics; 2) The natural history of HCV infection, including 'healthy individuals'; and 3) The areas for which more research is needed. A working group was created to assist the World Health organization (WHO) in estimating the GBD associated with HCV infection.

Chronic viral hepatitis as a public health issue in the world.

This article will focus on the impact caused by chronic viral hepatitis B and C globally and will discuss public health measures that have to be implemented in order to prevent and control these diseases. Chronic viral hepatitis is a major global public health problem, an important cause of morbidity and mortality from sequelae which include chronic hepatitis, cirrhosis and primary liver cancer. Being a 'silent' disease, the contribution of chronic hepatitis to global morbidity and mortality is generally underestimated. Hepatitis B and C prevention and control should seek to reduce both the incidence of new infections and the risk of chronic liver disease. A comprehensive public health prevention programme should include the prevention and detection of HBV and HCV infections, the diagnosis and control of viral hepatitis related chronic liver disease, conducting surveillance and monitoring the effectiveness of prevention activities, and setting up a research agenda.

Vaccine safety controversies and the future of vaccination programs.

In the years following the hepatitis B vaccination/multiple sclerosis controversy, a number of new issues regarding vaccine safety have been raised, in some cases leading to more debate and confusion. Against this background, an international group of experts was convened to review the current points of view concerning the use of thimerosal as a preservative and its potential risks; the suggested link between thimerosal-containing vaccines and acute lymphoblastic leukemia; the alleged association between aluminum-containing vaccines/macrophagic myofasciitis and general systemic complaints; a possible link between vaccination and autoimmune pathology; and a hypothetical link between measles-mumps-rubella vaccination and autism. At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine "scares" continue to have an international impact on immunization coverage. Creating a positive environment for immunization can be achieved by repositioning the value of vaccines and vaccination, supported by evidence-based information. The role of international organizations, the media, and the industry in the implementation of communication strategies was discussed and the impact of litigation issues on vaccination was evaluated. The Viral Hepatitis Prevention Board confirms its commitment to current recommendations for universal and risk group hepatitis B vaccination and further encourages the conduct of vaccine safety studies and the dissemination of their results.

Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants.

The long-term efficacy of hepatitis B vaccine, long-term effectiveness of hepatitis B immunisation programmes, immune memory induced by hepatitis B vaccine, current booster policies, and impact of hepatitis B virus mutants on immunisation programmes were reviewed at the Viral Hepatitis Prevention Board (VHPB) meeting in Sevilla, Spain, March 2004. The main focus was on universal vaccination programmes with data being presented from Italy, Saudi Arabia, Singapore, Spain, Taiwan, Thailand, The Gambia, and USA (Alaska).